This proposal requests the acquisition of a Bruker AVANCE III HD 500 MHz NMR spectrometer with a Prodigy (nitrogen-based) cryoprobe attachment and SampleCASE 24-position sample changer. This instrument is essential to address what is a looming crisis in NMR infrastructure at the University of Texas at Austin (UT Austin) due to both a lack of current capacity and the pending lack of support on the part of Agilent for the existing NMR spectrometers at UT Austin. This new, requested spectrometer with its two key accessories, will enable a number of capabilities that will advance biomedical research on the UT Austin campus. These include: 1) the highest sensitivity for a currently available 500 MHz instrument and one that is 2-3 times better than any existing NMR instrumentation at UT Austin for all nuclei from 15N to 31P. 2) Bruker automatic tuning, making changing nuclei and samples facile, and 3) a sample changer that permits users to submit their samples to a queue with automated sample loading, shimming, parameter optimization, probe tuning and data storage, thus enhancing efficiency. It is not an overstatement that NMR analyses are critical to all biomedical research being carried out at UT Austin that has at least some chemical component. NMR spectroscopy is used to confirm (or refute) that new molecules have been made as per design expectations and to analyze whether a given structure exists in the conformational form originally envisioned. NMR analyses are also critical to the development of new synthetic methodologies and are essential for understanding how a particular reagent or catalyst functions at the molecular level. NMR is also used to probe inter- and intramolecular interactions, thus allowing an understanding how, e.g., synthetic receptors and natural enzymes mediate their function. NMR is also critical to understanding complex biosynthetic pathways and the molecular nature of disease states. The current lack of NMR instrumental capacity is limiting progress on NIH-funded projects and stymieing emerging investigators from obtaining the data they need to compete successfully for NIH support. The requested NMR capabilities to UT Austin will not only address this deficit and the looming disaster associated with Agilent's decision to phase out support for existing spectrometers, it wil allow for an analytical capability that has not hitherto been seen on the UT Austin campus. This proposed acquisition will thus address existing problems, stave off pending ones, and allow for an overall enhancement in the level of NIH-supported biomedical research being carried out our university. The case for this instrument could not be more compelling.